摘要：

目的： 探讨E2F转录因子1（E2F transcription factor 1，E2F1）在口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）中的表达和临床意义，并阐明其在细胞凋亡和周期中的作用。方法： 基于R语言和癌症基因组图谱（the cancer genome atlas，TCGA）数据库分析OSCC中E2F1的表达和临床病理的相关性，通过基因集富集分析（gene set enrichment analysis，GSEA）发现E2F1参与的主要生物学过程。蛋白质印迹法（Western blotting）和实时定量聚合酶链反应（real-time quantitative polymerase chain reaction，RT-qPCR）检测E2F1在OSCC患者组织中的表达。通过细胞转染升高和敲低SCC15细胞系中E2F1的表达后，利用流式细胞术检测E2F1表达的改变对SCC15细胞凋亡和周期的影响。结果： E2F1在OSCC相关TCGA数据集中呈高表达，与T分期（T2或T4 vs T1）、组织学分级（G2或G3 vs G1）、临床分期（Ⅲ期vsⅠ期）、年龄（中年人vs青年人）和性别（男vs女）相关（P<0.05），多富集于细胞周期或核苷酸切除修复等基因组[P<0.05，错误发现率（false discovery rate，FDR）<0.25]。在37例OSCC患者组织中，E2F1的mRNA和蛋白均表达上调（P<0.001），表达上调的E2F1可降低SCC15细胞的凋亡率（P<0.05），以及在细胞周期中降低G1期的比率（P<0.01），并升高S期的比率（P<0.001）。结论： E2F1在OSCC中呈高表达，且可抑制细胞凋亡并促进细胞周期中G1/S期的转换。

关键词: 口腔鳞状细胞癌, E2F转录因子1, 生物信息学分析, 细胞凋亡, 细胞周期

Abstract:

Objective: To investigate the expression and clinical significance of E2F transcription factor 1 (E2F1) in oral squamous cell carcinoma (OSCC), and to analyze its function in apoptosis and cell cycle. Methods: The correlation between E2F1 expression and clinicopathology in OSCC was analyzed based on R language and The Cancer Genome Atlas (TCGA) database. The main biological processes involved in E2F1 were identified by gene set enrichment analysis (GSEA). Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect E2F1 expression in OSCC patients' tissue. After increasing and knocking down the expression of E2F1 in SCC15 cell lines by cell transfection, the effect of changes in E2F1 expression on apoptosis and cycle of SCC15 cells was analyzed by flow cytometry. Results: E2F1 was highly expressed in the OSCC-related TCGA dataset and correlated with T-stage (T2 or T4 vs T1), histological grade (G2 or G3 vs G1), clinical stage (Ⅲ vs I), age (middle vs young), and gender (male vs female) (P<0.05), which were mainly enriched in the genome of cell cycle or nucleotide excision repair [P<0.05 and false discovery rate (FDR) <0.25]. Both mRNA and protein expression of E2F1 were upregulated in the tissues of 37 OSCC patients (P<0.001). The expression of upregulated E2F1 decreased the rate of apoptosis in SCC15 cells (P<0.05), and also decreased the rate of G1 phase (P<0.01) and increased the rate of S phase (P<0.001) in the cell cycle. Conclusion: E2F1 is highly expressed in OSCC and can inhibit apoptosis and promote G1/S phase transition in the cell cycle.

Key words: oral squamous cell carcinoma, E2F transcription factor 1, bioinformatics analysis, apoptosis, cell cycle

中图分类号: 

• R782